Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion
Artikel i vetenskaplig tidskrift, 2005

To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.

metabolism

Mice

Knockout

Neural Cell Adhesion Molecules

Gene Expression Profiling

Mice

metabolism

Inbred C57BL

metabolism

Biological

Mice

Cell Transformation

RNA

Disease Progression

genetics

pathology

Neoplastic

genetics

Messenger

Animals

Reverse Transcriptase Polymerase Chain Reaction

Tumor Markers

metabolism

Insulinoma

genetics

Oligonucleotide Array Sequence Analysis

physiology

Extracellular Matrix Proteins

Författare

Joakim Håkansson

Göteborgs universitet

Xiaojie Xian

Göteborgs universitet

Liqun He

Göteborgs universitet

Anders Ståhlberg

Chalmers, Kemi- och bioteknik, Molekylär bioteknik

Sven Nelander

Göteborgs universitet

Tore Samuelsson

Göteborgs universitet

Mikael Kubista

Chalmers, Kemi- och bioteknik, Molekylär bioteknik

Henrik Semb

Göteborgs universitet

Tumor Biology

1010-4283 (ISSN) 1423-0380 (eISSN)

Vol. 26 2 103-112

Ämneskategorier

Biokemi och molekylärbiologi

MEDICIN OCH HÄLSOVETENSKAP

DOI

10.1159/000085817